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  2. Integrated serum pharmacochemistry with network pharmacology and pharmacological validation to elucidate the mechanism of yiqitongmai decoction (YQTMD) against myocardial infarction

Integrated serum pharmacochemistry with network pharmacology and pharmacological validation to elucidate the mechanism of yiqitongmai decoction (YQTMD) against myocardial infarction

  • J Ethnopharmacol. 2024 Sep 15:331:118329. doi: 10.1016/j.jep.2024.118329.
Hao Yu 1 Ning Wang 1 Xuerong Zhao 1 Lan Han 2 Jinyong Peng 3
Affiliations

Affiliations

  • 1 Institute of Intergrative Medicine, College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian, 116044, China.
  • 2 Department of Traditional Chinese Medicine Pharmacology, School of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, China. Electronic address: hanlan56@ahtcm.edu.cn.
  • 3 Institute of Intergrative Medicine, College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian, 116044, China; School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China; Hubei Shizhen Laboratory, Wuhan 430065, China. Electronic address: jinyongpeng2008@126.com.
Abstract

Ethnopharmacological relevance: Yiqitongmai decoction (YQTMD), a classic TCM, has been widely used in clinical treatment for MI. However, it is still difficult to clarify the potential active compounds and pharmacological mechanisms of it in treating MI.

Aim of the study: To explore the active ingredients, pharmacological effects, potential targets and mechanisms of YQTMD against MI.

Materials and methods: Serum pharmacochemistry by UPLC-MS/MS was applied to analyze the phytochemical components in serum from YQTMD. These components were then used to predict the potential targets using network pharmacology approach and molecular dynamics simulations, and then the protective effect of them on H9c2 cells following hypoxic conditions was assessed. Afterwards, the pharmacological effects of YQTMD on MI in mice were tested by determining electrocardiogram (ECG), echocardiography, cardiac biomarkers, oxidative stress, inflammation and pathophysiological changes. The protein levels involving STAT3 signal were detected using Western blot and immunofluorescence assays. Furthermore, STAT3 Inhibitor Sttatic was employed to further elucidate the underlying mechanisms.

Results: Totally, 26 compounds derived from YQTMD were identified in mice serum, and 201 genes associated with the compounds were collected. The compounds including safflomin A, ferulic acid, gypenoside XVII, ginsenoside Rg1 and glycyrrhizic acid were identified as the critical compounds of YQTMD to regulate STAT3 pathway. In vitro, compounds combination significantly enhanced the viability of H9c2 cells and reduced ROS level compared to model cells. The in vivo results showed that YQTMD effectively reduced myocardial injury, as evidenced by the decreased serum cardiac injury markers, reduction in the size of myocardial infarct, restoration of abnormal alterations in ECG and decrease in cardiomyocyte Apoptosis. Additionally, YQTMD attenuated MI-induced cardiac dysfunction, alleviated pathological changes, reduced MDA levels, and enhanced SOD and GSH levels compared with model mice. Significantly, the levels of IL-6, IL-1β, and TNF-α were observed to decrease in the YQTMD group. The expression levels of key proteins (p-STAT3, HIF-1α, NOX2, TLR5 and Caspase3) in STAT3 pathway were also regulated by YQTMD. However, the cardioprotective effects of YQTMD on MI were attenuated by STAT3 Inhibitor Sttatic.

Conclusions: This study investigated the active ingredients and potential mechanisms of YQTMD for MI treatment based on serum pharmacochemistry and network pharmacology approaches, revealing that YQTMD exerts its therapeutic effects on MI by alleviating oxidative stress, inflammation and Apoptosis through adjusting STAT3 signaling pathway.

Keywords

Myocardial infarction; Network pharmacology; STAT3 pathway; Serum pharmacochemistry; YQTMD.

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